AU2009248786B2 - Tricyclic nitrogen containing compounds and their use as antibacterials - Google Patents

Info

Publication number

AU2009248786B2

AU2009248786B2 AU2009248786A AU2009248786A AU2009248786B2 AU 2009248786 B2 AU2009248786 B2 AU 2009248786B2 AU 2009248786 A AU2009248786 A AU 2009248786A AU 2009248786 A AU2009248786 A AU 2009248786A AU 2009248786 B2 AU2009248786 B2 AU 2009248786B2

Authority

AU

Australia

Prior art keywords

mcthyl

methyl

dihydro

amino

pyridinyl

Prior art date

2008-05-23

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Ceased

Links

• Espacenet
• Global Dossier
• Discuss

• 230000000844 anti-bacterial effect Effects 0.000 title description 8
• 229940088710 antibiotic agent Drugs 0.000 title description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 250
• 150000003839 salts Chemical class 0.000 claims abstract description 39
• 238000000034 method Methods 0.000 claims abstract description 29
• 150000001204 N-oxides Chemical class 0.000 claims abstract description 27
• 201000008827 tuberculosis Diseases 0.000 claims abstract description 22
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
• 238000006243 chemical reaction Methods 0.000 claims description 93
• -1 5-chloro-6-methyl-3-pyridinyl Chemical group 0.000 claims description 81
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 77
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 50
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 42
• OPQFKYZLJABARW-UHFFFAOYSA-N 1,4,7-triazatricyclo[6.3.1.04,12]dodeca-2,6,8(12),9-tetraene-5,11-dione Chemical compound N1=CC(=O)N2C=CN3C(=O)C=CC1=C32 OPQFKYZLJABARW-UHFFFAOYSA-N 0.000 claims description 27
• 239000003814 drug Substances 0.000 claims description 22
• 241000124008 Mammalia Species 0.000 claims description 16
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• 125000004076 pyridyl group Chemical group 0.000 claims description 11
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• 150000001299 aldehydes Chemical group 0.000 claims description 6
• 125000003545 alkoxy group Chemical group 0.000 claims description 6
• 125000000217 alkyl group Chemical group 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000000335 thiazolyl group Chemical group 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 125000005997 bromomethyl group Chemical group 0.000 claims description 3
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
• HGSBYVOTCDHTLQ-UNTBIKODSA-N (3R)-3-[[4-[[5-methyl-6-(trifluoromethyl)pyridin-3-yl]methylamino]piperidin-1-yl]methyl]-1,4,7-triazatricyclo[6.3.1.04,12]dodeca-6,8(12),9-triene-5,11-dione hydrochloride Chemical compound Cl.N1=C(C(F)(F)F)C(C)=CC(CNC2CCN(C[C@H]3N4C=5N(C(C=CC=5N=CC4=O)=O)C3)CC2)=C1 HGSBYVOTCDHTLQ-UNTBIKODSA-N 0.000 claims description 2
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
• 238000006268 reductive amination reaction Methods 0.000 claims description 2
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 2
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims 1
• BIUDHHGROGJSHN-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethyl)benzaldehyde Chemical group FC1=CC=C(C=O)C=C1C(F)(F)F BIUDHHGROGJSHN-UHFFFAOYSA-N 0.000 claims 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
• 125000001475 halogen functional group Chemical group 0.000 claims 1
• QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical compound Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 claims 1
• 150000002500 ions Chemical class 0.000 claims 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims 1
• 125000003386 piperidinyl group Chemical group 0.000 claims 1
• 238000002560 therapeutic procedure Methods 0.000 abstract description 5
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 483
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 323
• 239000000203 mixture Substances 0.000 description 186
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 142
• 239000000243 solution Substances 0.000 description 140
• 239000007787 solid Substances 0.000 description 114
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 87
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 71
• 235000019439 ethyl acetate Nutrition 0.000 description 71
• 238000005481 NMR spectroscopy Methods 0.000 description 62
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 50
• 239000000047 product Substances 0.000 description 49
• 239000011541 reaction mixture Substances 0.000 description 44
• 230000002829 reductive effect Effects 0.000 description 43
• 239000003480 eluent Substances 0.000 description 41
• 238000002360 preparation method Methods 0.000 description 41
• 239000000741 silica gel Substances 0.000 description 40
• 229910002027 silica gel Inorganic materials 0.000 description 40
• 239000007858 starting material Substances 0.000 description 39
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
• 238000003818 flash chromatography Methods 0.000 description 35
• 238000000746 purification Methods 0.000 description 35
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
• 230000015572 biosynthetic process Effects 0.000 description 34
• 239000002904 solvent Substances 0.000 description 34
• 238000003786 synthesis reaction Methods 0.000 description 33
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 32
• 239000003921 oil Substances 0.000 description 32
• 235000019198 oils Nutrition 0.000 description 32
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 31
• 239000011734 sodium Substances 0.000 description 30
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 29
• 239000012074 organic phase Substances 0.000 description 28
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 239000000725 suspension Substances 0.000 description 27
• 229910052786 argon Inorganic materials 0.000 description 25
• 238000003756 stirring Methods 0.000 description 23
• 238000004128 high performance liquid chromatography Methods 0.000 description 21
• 239000012044 organic layer Substances 0.000 description 21
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
• 239000000706 filtrate Substances 0.000 description 20
• 229920006395 saturated elastomer Polymers 0.000 description 19
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 19
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
• 238000001914 filtration Methods 0.000 description 18
• 238000010992 reflux Methods 0.000 description 18
• 238000005160 1H NMR spectroscopy Methods 0.000 description 17
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
• 239000010410 layer Substances 0.000 description 15
• VASIZKWUTCETSD-UHFFFAOYSA-N manganese(II) oxide Inorganic materials [Mn]=O VASIZKWUTCETSD-UHFFFAOYSA-N 0.000 description 15
• HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 14
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 14
• 239000012267 brine Substances 0.000 description 14
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 14
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
• IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 13
• IAQWMWUKBQPOIY-UHFFFAOYSA-N chromium(4+);oxygen(2-) Chemical compound [O-2].[O-2].[Cr+4] IAQWMWUKBQPOIY-UHFFFAOYSA-N 0.000 description 12
• AYTAKQFHWFYBMA-UHFFFAOYSA-N chromium(IV) oxide Inorganic materials O=[Cr]=O AYTAKQFHWFYBMA-UHFFFAOYSA-N 0.000 description 12
• 238000004587 chromatography analysis Methods 0.000 description 11
• 239000012043 crude product Substances 0.000 description 11
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 11
• 229910000104 sodium hydride Inorganic materials 0.000 description 11
• CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 11
• 241000282414 Homo sapiens Species 0.000 description 10
• 150000001412 amines Chemical class 0.000 description 10
• 239000013058 crude material Substances 0.000 description 10
• 238000001035 drying Methods 0.000 description 10
• 238000009472 formulation Methods 0.000 description 10
• 239000012458 free base Substances 0.000 description 10
• 229910052739 hydrogen Inorganic materials 0.000 description 10
• 239000001257 hydrogen Substances 0.000 description 10
• 239000003208 petroleum Substances 0.000 description 10
• 239000000377 silicon dioxide Substances 0.000 description 10
• 229940124597 therapeutic agent Drugs 0.000 description 10
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
• 239000008346 aqueous phase Substances 0.000 description 9
• 239000000284 extract Substances 0.000 description 9
• 238000000605 extraction Methods 0.000 description 9
• 239000003960 organic solvent Substances 0.000 description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
• UKSUNUMFAOLDMK-UHFFFAOYSA-N 5-chloro-6-methylpyridine-3-carbaldehyde Chemical compound CC1=NC=C(C=O)C=C1Cl UKSUNUMFAOLDMK-UHFFFAOYSA-N 0.000 description 8
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
• 229940079593 drug Drugs 0.000 description 8
• 235000019441 ethanol Nutrition 0.000 description 8
• PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 8
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
• 239000011780 sodium chloride Substances 0.000 description 8
• 239000012312 sodium hydride Substances 0.000 description 8
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 8
• 239000003039 volatile agent Substances 0.000 description 8
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 7
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
• AIHIHVZYAAMDPM-QMMMGPOBSA-N [(2s)-oxiran-2-yl]methyl 3-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=CC(S(=O)(=O)OC[C@H]2OC2)=C1 AIHIHVZYAAMDPM-QMMMGPOBSA-N 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 239000007789 gas Substances 0.000 description 7
• 239000003981 vehicle Substances 0.000 description 7
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• 208000035143 Bacterial infection Diseases 0.000 description 6
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
• 208000022362 bacterial infectious disease Diseases 0.000 description 6
• 238000004440 column chromatography Methods 0.000 description 6
• 238000010438 heat treatment Methods 0.000 description 6
• 230000008569 process Effects 0.000 description 6
• 238000005406 washing Methods 0.000 description 6
• GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
• 229910021529 ammonia Inorganic materials 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 5
• 238000004296 chiral HPLC Methods 0.000 description 5
• 239000006071 cream Substances 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 150000002431 hydrogen Chemical class 0.000 description 5
• 229960003350 isoniazid Drugs 0.000 description 5
• QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 5
• 230000003647 oxidation Effects 0.000 description 5
• 238000007254 oxidation reaction Methods 0.000 description 5
• 229910052708 sodium Inorganic materials 0.000 description 5
• 239000012453 solvate Substances 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• FZDPHPXLTWCJAH-UNTBIKODSA-N (2r)-2-[(4-{[(5-chloro-6-methyl-3-pyridinyl)methyl]amino}-1-piperidinyl)methyl]-1,2-dihydro-3h,8h-2a,5,8a-triazaacenaphthylene-3,8-dione hydrochloride Chemical compound Cl.C1=C(Cl)C(C)=NC=C1CNC1CCN(C[C@H]2N3C=4N(C(C=CC=4N=CC3=O)=O)C2)CC1 FZDPHPXLTWCJAH-UNTBIKODSA-N 0.000 description 4
• ZOFUUOULXZPZHP-UHFFFAOYSA-N (5,6-dichloropyridin-3-yl)methanol Chemical compound OCC1=CN=C(Cl)C(Cl)=C1 ZOFUUOULXZPZHP-UHFFFAOYSA-N 0.000 description 4
• UVGILPAOAYLZIQ-UHFFFAOYSA-N (6-chloro-5-methylpyridin-3-yl)methanol Chemical compound CC1=CC(CO)=CN=C1Cl UVGILPAOAYLZIQ-UHFFFAOYSA-N 0.000 description 4
• QLCCYYUDSRQRFK-UHFFFAOYSA-N 3-(bromomethyl)-6-(trifluoromethyl)pyridazine Chemical compound FC(F)(F)C1=CC=C(CBr)N=N1 QLCCYYUDSRQRFK-UHFFFAOYSA-N 0.000 description 4
• BCHLMAIZUXPOET-UHFFFAOYSA-N 3-chloro-5-(hydroxymethyl)pyridine-2-carbonitrile Chemical compound OCC1=CN=C(C#N)C(Cl)=C1 BCHLMAIZUXPOET-UHFFFAOYSA-N 0.000 description 4
• YOKBWADWPYRVJS-UHFFFAOYSA-N 5-bromo-6-methylpyridine-3-carbaldehyde Chemical compound CC1=NC=C(C=O)C=C1Br YOKBWADWPYRVJS-UHFFFAOYSA-N 0.000 description 4
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 4
• 239000004677 Nylon Substances 0.000 description 4
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• 239000002253 acid Substances 0.000 description 4
• 230000002365 anti-tubercular Effects 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 4
• AEUTYOVWOVBAKS-UWVGGRQHSA-N ethambutol Chemical compound CC[C@@H](CO)NCCN[C@@H](CC)CO AEUTYOVWOVBAKS-UWVGGRQHSA-N 0.000 description 4
• 125000005843 halogen group Chemical group 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• PPNAOCWZXJOHFK-UHFFFAOYSA-N manganese(2+);oxygen(2-) Chemical compound [O-2].[Mn+2] PPNAOCWZXJOHFK-UHFFFAOYSA-N 0.000 description 4
• 239000012528 membrane Substances 0.000 description 4
• NGMLYTLMQBKQQJ-UHFFFAOYSA-N methyl 5-bromo-6-(trifluoromethyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(C(F)(F)F)C(Br)=C1 NGMLYTLMQBKQQJ-UHFFFAOYSA-N 0.000 description 4
• WINGWVOUOFMOJQ-UHFFFAOYSA-N methyl 5-bromo-6-chloropyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(Cl)C(Br)=C1 WINGWVOUOFMOJQ-UHFFFAOYSA-N 0.000 description 4
• WNPDQEDHQZXSOT-UHFFFAOYSA-N methyl 5-bromo-6-iodopyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(I)C(Br)=C1 WNPDQEDHQZXSOT-UHFFFAOYSA-N 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• 229920001778 nylon Polymers 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 4
• 238000012799 strong cation exchange Methods 0.000 description 4
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 4
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
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